Biomedical subjects

D Mavroudis

Publications and source records attributed to D Mavroudis.

At least 19 recordsLinked to original sources

PubMed2007

An improved method for the diagnostic approach of alpha+-thalassaemia.

An improved method for the diagnostic approach of alpha(+)-thalassaemia is described. The method is based on five common parameters: absence of iron deficiency, mild morphological abnormalities of erythrocytes, normal or slightly reduced erythrocytic indices MCV and MCH, normal chromatographic findings, and presence of haemoglobin H inclusions in erythrocytes with methyl-violet stain after, but not before, incubation with oxidant agent. We studied by DNA analysis, 58 subjects fulfilling the above mentioned diagnostic criteria and we found that 50 of them (86.2%) had a alpha-globin gene defect. In the remaining eight subjects (13.8%) no alpha-gene defect could be documented with the techniques used in the DNA analysis, which detect the six well-known alpha(+)-thalassaemic defects in the Greek population. We conclude that the improved method, we described has a high sensitivity and accuracy in the screening of alpha(+)-thalassaemia.

Adolescent↗

PubMed2006

Phase II trial of capecitabine and oxaliplatin (CAPOX) plus cetuximab in patients with metastatic colorectal cancer who progressed after oxaliplatin-based chemotherapy.

BACKGROUND: Cetuximab is an IgG1 monoclonal antibody targeting the epidermal growth factor receptor and is able to reverse the resistance to irinotecan in patients with metastatic colorectal cancer (mCRC). This phase II trial evaluates the safety and efficacy of cetuximab combined with capecitabine and oxaliplatin (CAPOX) in the treatment of patients with mCRC progressing under oxaliplatin-based chemotherapy. PATIENTS AND TREATMENT: Forty patients with mCRC were treated with cetuximab (loading dose 400 mg/m(2) and then 250 mg/m(2) i.v. weekly) in combination with CAPOX (d(1): L-OHP 85 mg/m(2) and d(1-7) capecitabine 2000 mg/m(2) every 2 weeks). Thirty-one (77.5%) and nine (22.5%) patients had oxaliplatin-refractory and -resistant disease, respectively; in addition, 32 (80%) patients had also progressed on prior irinotecan-based chemotherapy. RESULTS: One hundred and thirty-four cycles were administered (median of four cycles per patient). Main toxic effects included grade 3-4 neutropenia (12.5%), grade 3/4 diarrhea (7.5%), grade 3 fatigue (2.5%), and grade 2-3 neurotoxicity (22.5%). One (2.5%) complete and seven (17.5%) partial responses were achieved [overall objective response rate (ORR): 20%; 95% confidence interval (CI): 9% to 32%)], whereas 11 (27.5%) patients had stable disease [disease control rate (DCR): 47.5%; 95% CI: 30.2% to 64.5%]. The ORR and DCR were 18.7% and 46.8%, respectively, in patients with oxaliplatin-refractory disease. The median time to tumor progression was 3 months, the median survival 10.7 months and the probability of 1-year survival rate 53.4%. CONCLUSIONS: The combination of cetuximab plus CAPOX is safe and has a promising activity in patients with mCRC refractory or resistant to oxaliplatin.

Adenocarcinoma↗

PubMed2006

Sequential administration of docetaxel followed by maintenance gefitinib, as salvage treatment in patients with advanced NSCLC: a multicenter phase II trial.

PURPOSE: To evaluate the activity and toxicity of the sequential administration of docetaxel followed by gefitinib in patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND TREATMENT: Forty-one patients pre-treated with at least one prior chemotherapy regimen (platinum- or taxane-based) for advanced/metastatic NSCLC received three cycles of docetaxel 30 mg/m2, administered as a 1-h IV infusion, on days 1, 8 and 15 of each 4-week cycle followed by gefitinib 250 mg daily po. Gefitinib treatment was continued until disease progression, development of unacceptable toxicity, or withdrawal of patients consent. RESULTS: Two (4.9%) patients achieved a partial response and 10 (24.4%) stable disease, for a disease control rate of 29.3% (95% CI: 15.3%-43.2%) while on weekly docetaxel treatment. Additionally, progressive disease (PD) was observed in 29 (70.7%). No objective responses were observed during the gefitinib maintenance therapy; however, 17 (41.5%) patients presented stable disease maintained for more than 2 months. Median time to progression was 3.0 months (range: 1-38.3 months; 95% CI: 2.4-3.6); median overall survival 6.9 months (range: 1.2-40.2 months; 95% CI: 5.34-8.52) while the 1-year survival was 28.8%. Therapy was generally well tolerated with diarrhea and rash being the most frequent toxicities. CONCLUSIONS: The sequential administration of docetaxel and gefitinib was well tolerated and moderately active against advanced pre-treated NSCLC.

Adult↗

PubMed2006

Salvage chemotherapy with gemcitabine and oxaliplatin in heavily pretreated patients with metastatic breast cancer: a multicenter phase II study.

PURPOSE: It was the aim of this study to evaluate the activity and tolerance of gemcitabine and oxaliplatin in pretreated metastatic breast cancer patients. METHODS: Thirty-one patients who had disease relapse or progression after completion of an anthracycline- and/or taxane-based front-line regimen were treated with gemcitabine 1,500 mg/m(2) on days 1 and 8 as a 30-min intravenous infusion and oxaliplatin 130 mg/m(2) on day 8 as a 4-hour intravenous infusion, in cycles of 21 days. RESULTS: Complete response occurred in 1 patient (3%) and partial response in 4 patients (13%) (overall response rate 16%; 95% confidence interval 3.2-29.1). Nine patients (29%) had stable disease and 17 (55%) progressive disease. Three partial responses (13%) were achieved among 23 patients receiving the regimen as third-line treatment. The median duration of response was 6 months (range 3-44.8), the median time to tumor progression 4.6 months (range 0.8-43.8), and the median survival 14.4 months (range 2.1-44.8). Grade 3 and 4 neutropenia occurred in 14 patients (45%), grade 3 and 4 thrombocytopenia in 6 patients (20%), and grade 2 and 3 asthenia in 4 patients (13%). There was no episode of febrile neutropenia. CONCLUSION: The gemcitabine-oxaliplatin combination is a relatively active and well-tolerated salvage regimen in patients with heavily pretreated metastatic breast cancer.

Aged↗

PubMed2006

A phase I study of the optimized cryptic peptide TERT(572y) in patients with advanced malignancies.

OBJECTIVE: It was the aim of this study to evaluate the safety of the optimized cryptic peptide TERT(572Y) in pretreated patients with advanced cancer. METHODS: Nineteen patients with progressive and chemotherapy-refractory tumors received escalated doses (2-6 mg) of 2 subcutaneous injections of the optimized TERT(572Y) peptide followed by 4 subcutaneous injections of the native TERT(572) peptide every 3 weeks. Both TERT peptides were coinjected with adjuvant Montanide ISA51. Toxicity was evaluated every 3 weeks and peptide-specific CD8+ cells were detected by flow cytometry using TERT(572Y) tetramers. RESULTS: Fourteen out of 19 patients completed the vaccination program. No grade III/IV toxicity was observed. Grade I anemia was observed in 4 patients and local skin reaction at the injection site in 11 patients. Other nonhematologic toxicities were mild, and no late toxicity was observed after a median postvaccination follow-up period of 10.7 months. There was no dose-limiting toxicity. Peripheral blood TERT(572Y)-specific CD8+ lymphocytes were detected in 13 out of 14 evaluable patients after 2 injections with the optimized TERT(572Y) peptide. There was no complete or partial response, but 4 patients (21%) with persistent TERT(572Y)-specific CD8+ experienced stable disease for a median of 10.5 months. CONCLUSION: TERT(572Y) peptide vaccine is well tolerated and effective in eliciting specific TERT(572Y) CD8+ lymphocytes in pretreated cancer patients, demonstrating that cryptic peptides could be used in cancer immunotherapy.

Adjuvants, Immunologic↗

PubMed2006

Sequential gemcitabine and cisplatin followed by docetaxel as first-line treatment of advanced urothelial carcinoma: a multicenter phase II study of the Hellenic Oncology Research Group.

BACKGROUND: The purpose of this study was to investigate the toxicity and efficacy of the sequential administration of gemcitabine (GMB) in combination with cisplatin (CDDP) followed by docetaxel (Taxotere) as first-line treatment of advanced urothelial carcinoma. PATIENTS AND METHODS: Patients [aged </=70 years and performance status (PS) (Eastern Cooperative Oncology Group) 0-2] with previously untreated locally advanced/recurrent or metastatic urothelial carcinoma were eligible. Study treatment consisted of GMB (1000 mg/m(2), days 1 and 8) and CDDP (70 mg/m(2), day 1) (GP regimen), every 21 days for a total of four cycles followed by docetaxel (D; 100 mg/m(2), day 1) every 21 days for four cycles. RESULTS: Thirty-eight patients with a median age of 67 years were enrolled; 67% of them had PS 0 and 87% stage IV disease. Patients received a median of four GP and four D cycles per patient. Grade 3-4 neutropenia occurred in 27% and 63% patients with GP and D, respectively. Grade 3-4 thrombocytopenia occurred in 11% of patients, only with the GP regimen. Other toxic effects were mild. There was no toxic death. The objective response rate was 55.2% [95% CI: 39.45%-71.07%]. Five patients had complete response (13.15%) and 16 patients had partial response (42.1%), while nine patients had disease stabilization (23.7%) (intention-to-treat analysis). After a median follow-up period of 13 months (range 1.5-40.5 months), the median time to progression was 6.8 months (range 1-40.5 months), the median overall survival 13 months (range 1.5-40.5 months), and the 1-year survival rate 55.3%. CONCLUSION: The sequential administration of GP followed by D is active and well tolerated as first-line treatment of advanced urothelial carcinoma and merits to be further evaluated.

Adult↗

PubMed2006

FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin and irinotecan) vs FOLFIRI (folinic acid, 5-fluorouracil and irinotecan) as first-line treatment in metastatic colorectal cancer (MCC): a multicentre randomised phase III trial from the Hellenic Oncology Research Group (HORG).

To compare the efficacy and toxicity of oxaliplatin (L-OHP) in combination with irinotecan (CPT-11), 5-fluorouracil (5-FU) and leucovorin (LV) (FOLFOXIRI) vs irinotecan and 5-FU/LV (FOLFIRI) as first-line treatment of patients with metastatic colorectal cancer (MCC). A total of 283 chemotherapy-naïve patients with MCC were enrolled (FOLFIRI arm: n=146; FOLFOXIRI arm: n=137). In the FOLFOXIRI arm, CPT-11 (150 mg m(-2)) was given on d1, L-OHP (65 mg m(-2)) on d2, LV (200 mg m(-2)) on days 2 and 3 and 5-FU (400 mg m(-2) as i.v. bolus and 600 mg m(-2) as 22 h i.v. continuous infusion) on days 2 and 3. In the FOLFIRI arm, CPT-11 (180 mg m(-2)) was given on d1 whereas LV and 5-FU were administered in the same way as in the FOLFOXIRI regimen. Both regimens were administered every 2 weeks. There was no difference in terms of overall survival (median OS: 19.5 and 21.5 months, for FOLFIRI and FOLFOXIRI, respectively; P=0.337), median time to disease progression (FOLFIRI: 6.9 and FOLFOXIRI: 8.4 months; P=0.17), response rates (33.6 and 43% for FOLFIRI and FOLFOXIRI, respectively; P=0.168). Patients treated with FOLFOXIRI had a significantly higher incidence of alopecia (P=0.0001), diarrhoea (P=0.0001) and neurosensory toxicity (P=0.001) compared with patients treated with FOLFIRI. The present study failed to demonstrate any superiority of the FOLFOXIRI combination compared with the FOLFIRI regimen, although the observed median OS is one of the best ever reported in the literature.

Adenocarcinoma↗

PubMed2006

Native valve Aspergillus endocarditis in two patients with aplastic anaemia.

Native valve fungal endocarditis is an uncommon disease with a high mortality rate. We present the clinical features, histological findings and outcome of 2 patients with native valve Aspergillus endocarditis. Both patients had aplastic anaemia as a predisposing disease. The diagnosis was made by Duke's criteria in 1 case and by histology in the other. Surgery was precluded owing to profound thrombocytopenia. Both patients had fatal outcome despite administration of liposomal amphotericin beta.

Adolescent↗

PubMed2005

Combination of irinotecan (CPT-11) plus 5-fluorouracil and leucovorin (FOLFIRI regimen) as first line treatment for elderly patients with metastatic colorectal cancer: a phase II trial.

PURPOSE: To evaluate the efficacy and tolerance of irinotecan (CPT-11) in combination with bolus and continuous infusion of 5-fluorouracil (5-FU) and leucovorin (LV) (FOLFIRI regimen) as first-line treatment of elderly patients with metastatic colorectal cancer (MCC). METHODS: Thirty consecutive, previously untreated patients with metastatic colorectal cancer, aged (median 76 years; range 70-84) were enrolled. The performance status (WHO) was 0 in 8, 1 in 16 and 2 in 6 patients; 19 (63%) patients had prior surgery and 8 (27%) adjuvant chemotherapy. CPT-11 (180 mg/m(2) as a 90 min i.v. infusion) was administered on day 1, LV (200 mg/m(2) as a 2-hour i.v. infusion), 5-FU (400 mg/m(2)/d i.v. bolus followed by 600 mg/m(2)/d as a 22-hour i.v. continuous infusion) were given on days 1 and 2 every 2 weeks. RESULTS: Complete response was achieved in one (3.3%) patient and partial response in 10 (33.3%) (overall response rate: 36.6%; 95% C.I.: 26.6-48.4%); 11 (36.6%) patients had stable disease and, 8 (26.6%) disease progression. The median duration of response was 7.5 months and the median time to disease progression 7.0 months. After a median follow-up period of 17 months, the median overall survival was 14.5 months. Main toxicities were: grade 3-4 neutropenia (n = 6; 20%), grade 3 thrombocytopenia (n = 1; 3.3%), grade 2 anemia (n = 9; 30%), grade 3-4 diarrhea (n = 5; 17%) and grade 3 asthenia (n = 3; 10%). There was one treatment-related death due to neutropenic sepsis. CONCLUSIONS: The FOLFIRI combination is an active regimen with manageable toxicity as front-line treatment in patients above 70 years of age.

Aged↗

PubMed2005

Second-line treatment with irinotecan plus cisplatin vs cisplatin of patients with advanced non-small-cell lung cancer pretreated with taxanes and gemcitabine: a multicenter randomised phase II study.

The aim of this study was to compare the irinotecan/cisplatin regimen with cisplatin as second-line chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC) pretreated with a taxane/gemcitabine regimen. Patients (n = 147) with stage IV NSCLC pretreated with a taxane/gemcitabine regimen were randomly assigned to receive either irinotecan (110 mg m(-2), day 1 and 100 mg m(-2), day 8) and cisplatin (80 mg m(-2), day 8) (IC; n = 74) or CDDP (80 mg m(-2), day 1) (C; n = 73) every 3 weeks. Patients treated with IC and C had a median survival of 7.8 and 8.8 months, respectively (P = 0.933). The 1-year survival rate was 34.3% for IC-treated patients and 31.7% for C-treated patients. Cox's regression analysis revealed that response to treatment (hazard ratio (HR) = 2.787; 95% confidence interval (CI): 1.1578-4.922) and performance status (HR = 1.865; 95% CI: 1.199-2.872) was independent prognostic factors for survival. Overall response rate was 22.5% (95% CI: 12.8-32.2%) for IC-treated patients and 7.0% (95% CI: 1.15-13.6%) for C-treated patients (P = 0.012); tumour growth control (partial remission (PR) + stable disease (SD)) was observed in 26 (38%) IC and 25 (36%) C patients (P = 0.878). There was no difference in terms of quality of life between the two chemotherapy arms. The incidence of febrile neutropenia, grade 3 and 4 neutropenia and grade 3 and 4 diarrhoea was significantly higher in the IC- than the C-treated patients. Other toxicities were mild. There were no treatment-related deaths in either arm. The IC regimen did not confer a survival benefit compared with C as second-line treatment of patients with advanced NSCLC pretreated with a taxane/gemcitabine regimen, despite its better efficacy in terms of response rate.

Adult↗

PubMed2005

Detection of CK-19 mRNA-positive cells in the peripheral blood of breast cancer patients with histologically and immunohistochemically negative axillary lymph nodes.

BACKGROUND: To investigate the incidence of direct hematogenous spread of cancer cells in patients with early-stage breast cancer by studying the presence of occult tumor cytokeratin-19 (CK-19) mRNA(+) cells in the peripheral blood in relation to the status of sentinel (SLNs) and (ALNs) axillary lymph nodes. PATIENTS AND METHODS: SLNs and ALNs from 111 patients with operable stage I-II breast adenocarcinoma were evaluated for the presence of tumor cells by hematoxylin-eosin (H&E) staining and, if negative, by immunohistochemistry (IHC) using an anti-CK-19 antibody. Peripheral blood was also analyzed for the presence of CK-19 mRNA(+) cells by nested RT-PCR, before the initiation of adjuvant treatment and in CK-19 mRNA(+) patients following the completion of adjuvant chemotherapy and hormonal treatment. RESULTS: After both H&E staining and IHC analysis, 29 (26%) patients were ALN negative (N0). In 78 (70%) patients H&E staining and in four (3.6%) IHC analysis revealed tumors cells, and these patients were considered as ALN positive (N+). Peripheral blood CK-19 mRNA(+) cells were detected in nine (31%) out of 29 N0 and in 31 (38%) out of 82 N + patients (P=0.5) before any adjuvant treatment. Adjuvant chemotherapy and hormone treatment resulted in the disappearance of the CK-19 mRNA(+) cells in all N0 patients and in 15 out of 31 N + patients. After a median follow-up of 40 months, all the N0 CK-19 mRNA(+) patients were relapse-free whereas four (13%) N + CK-19 mRNA(+) patients had relapsed. CONCLUSIONS: Direct hematogenous dissemination of occult tumor cells may occur in a substantial proportion of patients with early-stage breast cancer. The prognostic implication of the detection of these cells requires long follow-up periods and further studies.

Adenocarcinoma↗

PubMed2004

Bloodstream infections in patients with solid tumors: associated factors, microbial spectrum and outcome.

BACKGROUND: Although patients with malignant diseases are at increased risk for bloodstream infections (BSIs), limited data are available for those with solid tumors. PATIENTS AND METHODS: The etiology, clinical features and outcome of BSIs were retrospectively studied in patients with solid tumors treated at the Department of Medical Oncology at the University Hospital of Heraklion, Greece, from November 1995 through June 2000. RESULTS: A total of 157 episodes of BSIs was identified among 137 patients over the study period. The majority of the episodes (128; 82%) occurred in non-neutropenic patients. 80 of 157 (51%) of the episodes were healthcare-associated, 35% (55 of 157) were nosocomial and 14% (22 of 157) were community acquired. A single pathogen was isolated in 86% of the episodes. A total of 184 pathogens was isolated (51% gram-negative rods, 44% gram-positive cocci, 3% anaerobes and 3% fungi), while the portal of entry was identified in 104 of 157 (66%) of the episodes. The site of the primary tumor or the metastases were the source of BSI in 39 of 104 (37.5%) of the episodes with an identified source. The overall infectious mortality was 20% and was significantly higher when the initial empirical antibiotic therapy was inappropriate (39%; p < 0.001) and in the presence of shock (63%; p < 0.001). CONCLUSION: BSIs in patients with solid tumors are frequently healthcare associated and in a large percentage the portal of entry can be identified. Neutropenia is not as common as in patients with hematologic malignancies. Inappropriate initial empirical antibiotic therapy and shock are clinical factors associated with worse outcomes.

Adolescent↗

PubMed2004

Dose escalation study on oxaliplatin and capecitabine (Xeloda) in patients with advanced solid tumors.

OBJECTIVES: Capecitabine (CAP) and oxaliplatin (OX) have shown interesting activity in a wide range of solid tumors. A phase I study was conducted in order to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of their combination in patients with refractory solid tumors. PATIENTS AND METHODS: Thirty-three pretreated patients with histologically confirmed inoperable neoplasms were enrolled. The patients' median age was 64 years, 21 were males, and 27 had a WHO performance status of 0-1. OX was administered on days 1 and 8, as a 3-hour intravenous infusion, at escalated doses ranging from 50 to 70 mg/m(2). CAP was administered orally for 14 consecutive days, at escalated doses ranging from 1,200 to 2,100 mg/m(2)/day. Treatment was repeated every 3 weeks. RESULTS: At the dose of 2,100 mg/m(2) (Xeloda) and 70 mg/m(2) (OX), all 3 enrolled patients presented DLT (grade 3 diarrhea, grade 3 asthenia and grade 3 neurotoxicity, respectively), and, thus, the recommended MTD for future phase II studies are 2,000 mg/m(2) for CAP and 70 mg/m(2 )for OX. A total of 145 treatment cycles were administered. Toxicity was very mild. Grade 2/3 neutropenia was observed in 4 (3%) treatment cycles. The main nonhematologic toxicities were grade 2/3 nausea/vomiting (7 cycles; 5%), grade 2/3 neurotoxicity (10 cycles; 7%), grade 2/3 asthenia (8 cycles; 5.5%) and grade 2/3 diarrhea (6 cycles; 4%). There was no treatment-related death. One (4%) complete remission, 2 (8%) partial remissions, and 9 (36%) cases of stable disease were observed among 25 evaluable patients. CONCLUSIONS: The results demonstrate that CAP and OX can be safely combined at clinically relevant doses and that this regimen merits further evaluation.

Aged↗

PubMed2004

Front-line chemotherapy with docetaxel and gemcitabine administered every two weeks in patients with metastatic breast cancer: a multicenter phase II study.

OBJECTIVE: To evaluate the docetaxel-gemcitabine combination administered every 2 weeks in women with untreated metastatic breast cancer (MBC). METHODS: Fifty-two patients with MBC received docetaxel 65 mg/m2 as front-line chemotherapy intravenously over 1 h followed by gemcitabine 1,500 mg/m2 intravenously over 30 min on days 1 and 14. Cycles were repeated every 28 days without prophylactic growth factor support. Twenty-eight (54%) patients had previously received chemotherapy as adjuvant or neoadjuvant treatment. Thirty-six (69%) patients had visceral disease including 20 (38%) with liver metastases. All patients were evaluated for toxicity and 45 for response. RESULTS: In an intention-to-treat analysis, a complete response occurred in 7 (13%) patients and partial response in 24 (46%) for an overall response rate of 59% (95% CI: 46.3-73.0%). The response rate was 68% for the 28 patients who had previously received adjuvant or neoadjuvant chemotherapy and 67% for the 36 patients with visceral metastases. The median duration of response was 6.1 months and the median time to disease progression 10.9 months. A total of 254 cycles were administered with dose reduction in 26 (10%) cycles and no lethal toxicity. Grade III-IV neutropenia occurred in 17 (33%) patients and thrombocytopenia in 3 (6%). Febrile neutropenia developed in 3 (6%) patients. Nonhematological toxicity was generally mild. CONCLUSION: The docetaxel-gemcitabine combination is an active and well-tolerated front-line treatment for patients with MBC. This regimen represents a suitable option especially for women relapsing after anthracycline-based adjuvant chemotherapy.

Adult↗

PubMed2003

Sequential administration of cisplatin-etoposide followed by topotecan in patients with extensive stage small cell lung cancer. A multicenter phase II study.

PURPOSE: To evaluate the activity of the sequential administration of cisplatin-etoposide (PE) followed by topotecan (TOP) in patients with extensive stage small cell lung cancer (SCLC). PATIENTS AND METHODS: Previously untreated patients with extensive stage SCLC received 4 cycles of cisplatin 75 mg/m(2) IV on day 1 and etoposide 100 mg/m(2) IV on days 1-3 every 21 days followed by 4 cycles of TOP 1.5 mg/m(2) IV on days 1-5 every 21 days. RESULTS: Thirty-eight patients were entered in the study. Their median age was 63 years and the performance status (WHO) was 0 for 5, 1 for 25 and 2 for 8 patients. All patients were evaluable for toxicity and 32 for response to PE and 25 to TOP. Of the 38 patients receiving PE, 1 (3%) patient achieved complete response (CR) and 17 (45%) partial responses (PR) for an overall response rate to PE of 47% (95% confidence interval: 36.7-68.5%). Four (23.5%) of the 17 patients with PR after PE, achieved CR with TOP. None of the patients with stable or progressive disease after PE responded to TOP. The response rate of the 27 patients receiving TOP following PE was 15% (95% confidence interval: 1.4-28.2%). After a median follow up of 9 months, the median duration of response was 6.5 months, the time to tumor progression 6.5 months, the median survival 8.5 months and the 1-year survival 34%. A total of 136 cycles of PE and 89 cycles of TOP have been administered with a median of 4 cycles/patient for each regimen. There were 2 toxic deaths after PE associated with grade IV febrile neutropenia. Treatment delays due to toxicity occurred in 17 (12%) cycles of PE and 20 (22%) cycles of TOP while doses were reduced in 7 (5%) and 4 (4%) cycles, respectively. Grade 3-4 neutropenia, thrombocytopenia and febrile neutropenia occurred in 24, 2 and 3% of PE cycles and 21, 12 and 1% of TOP. Non-hematologic toxicity was mild. The delivered dose intensity was 100% for PE and 93% for TOP. CONCLUSIONS: The sequential administration of TOP after PE is associated with manageable toxicity and may increase the number of CRs in patients with chemosensitive extensive stage SCLC. However, based on this data and the lack of survival benefit in a previous phase III study, the sequential regimen should not be used outside of a clinical trial.

Adult↗

PubMed2003

ZD1839, a novel, oral epidermal growth factor receptor-tyrosine kinase inhibitor, as salvage treatment in patients with advanced non-small cell lung cancer. Experience from a single center participating in a compassionate use program.

OBJECTIVE: We evaluated the efficacy and tolerability of the orally active, selective epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) ZD1839 in patients with pretreated advanced non-small cell lung cancer (NSCLC) participating in a compassionate use program. PATIENTS AND METHODS: Thirty-one patients with advanced, unresectable and progressive NSCLC, previously treated with one or two chemotherapy regimens, received ZD1839 250 mg orally once daily. Patients who had received only one prior chemotherapy regimen had to be considered unsuitable for second-line chemotherapy. RESULTS: The disease control rate was 32% (95% CI: 15.8-48.7) (1/31 patients had a partial response and 9/31 patients had stable disease) and the median overall survival 23 weeks (range 4-40). Symptom improvement was reported by 39% of patients overall and by 83% of patients who achieved disease control. The median time to symptom improvement was 3 weeks (range 2-4). Adverse events were generally mild (grade I or II) and reversible and consisted mostly of skin rash, diarrhea and fatigue. CONCLUSIONS: ZD1839 demonstrated clinically meaningful antitumor activity with significant improvement in symptoms in this heavily pretreated group of patients with advanced NSCLC. Furthermore, ZD1839 showed a favorable toxicity profile, with the majority of adverse events being mild and reversible.

Administration, Oral↗

PubMed2003

A dose-escalation and pharmacokinetic study of gemcitabine and oxaliplatin in patients with advanced solid tumors.

BACKGROUND: Gemcitabine and oxaliplatin have broad antineoplastic activity and favorable toxicity. We conducted a phase I study to determine the maximum tolerated doses (MTDs) and dose-limiting toxicities (DLTs) of the combination in patients with advanced solid tumors. PATIENTS AND METHODS: Sixty-eight patients with advanced stage solid tumors were enrolled. Treatment was first-line for 35% of patients, second-line for 27%, and third-line for 38%. Gemcitabine was administered at escalating doses of 1000-2000 mg/m(2) as a 30-min intravenous (i.v.) infusion on days 1 and 8 and oxaliplatin at 60-130 mg/m(2) as a 4-h i.v. infusion on day 8 every 21 days without growth factor support. RESULTS: The MTD was defined at gemcitabine 1800 mg/m(2) on days 1 and 8 and oxaliplatin 130 mg/m(2) on day 8. Twelve dose levels were evaluated and DLTs occurring during the first cycle consisted of grade 4 neutropenia, grade 3 asthenia or mucositis and grade 1-3 neutropenia or thrombocytopenia resulting in treatment delays. A total of 266 cycles were administered with only one episode of febrile neutropenia and no toxic deaths. Seven (3%) and 26 (10%) cycles were complicated by grade 4 and 3 neutropenia, respectively, three (1%) and 13 (5%) by grade 4 and 3 thrombocytopenia, and eight (3%) by grade 3 anemia. The most common non-hematological toxicity was grade 2/3 asthenia observed in 23% of cycles. Responses were observed in patients with a variety of epithelial neoplasms. The pharmacokinetic study revealed no significant interaction between the two drugs. CONCLUSIONS: The combination of gemcitabine and oxaliplatin has excellent tolerability and promising activity in patients with advanced solid tumors. As the MTD exceeds the recommended single-agent dose for gemcitabine, and a dose-response effect has not been established, we recommend using both drugs at full doses, e.g. gemcitabine 1200-1400 mg/m(2) on days 1 and 8 and oxaliplatin 130 mg/m(2) on day 8 for further phase II studies.

Adult↗

PubMed2003

Peripheral blood circulating cytokeratin-19 mRNA-positive cells after the completion of adjuvant chemotherapy in patients with operable breast cancer.

BACKGROUND: The purpose of this study was to evaluate the prognostic significance of the molecular detection of cytokeratin 19 (CK-19) mRNA-positive cells in the peripheral blood of women with operable breast cancer after the completion of adjuvant chemotherapy. PATIENTS AND METHODS: Blood from 161 patients with stage I and II breast cancer, obtained after the completion of adjuvant chemotherapy, was tested by nested RT-PCR for CK-19 mRNA detection. Using univariate and multivariate analyses possible interactions with other prognostic factors and association of CK-19 mRNA detection with risk of relapse, disease-free interval (DFI) and overall survival were investigated. RESULTS: After completion of adjuvant chemotherapy, 27.3% of patients had peripheral blood CK-19 mRNA-positive cells; there was no association of this finding with any other prognostic factors or the type of chemotherapy regimen used. For patients with less than four involved axillary lymph nodes the risk of relapse was 3.81 [95% confidence interval (CI) 1.06-13.71] times higher, and the DFI was significantly reduced (P = 0.028) if CK-19 mRNA-positive cells were detectable in the blood after the completion of adjuvant chemotherapy. In contrast, for patients with four or more involved lymph nodes, the presence of CK-19 mRNA-positive cells after adjuvant chemotherapy did not significantly affect the risk of relapse or DFI. Furthermore, the risk of relapse was higher (hazards ratio 3.70; 95% CI 1.09-13.89) and the DFI was reduced (P = 0.022) for patients with detectable CK-19 mRNA-positive cells following adjuvant cyclophosphamide, methotrexate and 5-fluorouracil (CMF) as compared with epirubicin, cyclophosphamide and 5-fluorouracil (FEC) or sequential taxotere-epirubicin and cyclophosphamide (T/EC) chemotherapy. CONCLUSIONS: The detection of CK-19 mRNA-positive cells in the peripheral blood after adjuvant chemotherapy may be of clinical relevance for patients with early breast cancer and less than four involved axillary lymph nodes.

Adult↗